Low dose rate brachytherapy either alone or in combination with external irradiation, has been the treatment of choice in the management of a number of human cancers. One of the major advantages of low dose rate brachytherapy is the physical dose distribution permitting delivery of higher total dose at a higher dose rate to the tumor than to the normal tissues, resulting in an improved therapeutic ratio. Radiobiologically, reduced oxygen enhancement ratios (OER) and reoxygenation may also be advantages of low dose rate brachytherapy There is reason to believe thatthe physical and radiobiological advantages of low dose rate irradiation can be enhanced even more by chemical modifiers. The proposed studies are designed to obtain quantitative information on the modification of the effects of low dose rate irradiation on tumors and normal tissue by radiosensitizers, radioprotectors, and chemotherapeutic agents and to provide a rational basis for clinical trials using these compound in combination with low dose rate brachytherapy. The effects of low dose rate irradiation and drug alone or in combination will be evaluated as a function of dose rate, drug dose and time of administration in 3 murine tumors: EMT6/SF, SQ1, and Line-1 tumors. Quantitative endpoints will include in vitro cell survival and tumor growth delay as well as the jejunal crypt cell survaval assay. For each combined treatment the dose effect factors (DEF's) for the tumors as well as the normal tissue and the therapeutic ratio will be determined. In addition, the degree of reoxygenation during continuous low dose rate irradiation will be determined for each tumor.